In 1998, the World Health Organization (WHO) estimated there would be 300 million people globally living with type 2 diabetes mellitus (T2DM) by 2025.1 In 2017, the actual figures were
462 million (6.28% of the world’s population) well surpassing the estimations eight years earlier, with a projected increase of 7,079 people diagnosed per 100,000 by 2030. T2DM prevalence is continuing to rise at a rapid rate and continues to be a serious public health consideration.2
The common risk factors for this metabolic condition caused by impaired glucose tolerance leading to insulin resistance include genetic predisposition, age, and lifestyle factors, such as diet and physical activity levels.1,2 In the last decade an increasing amount of research has focussed on the impact of sleep dysregulation as a prominent factor for metabolic health and T2DM development.1
Sleep: a metabolic regulator
Sleep is a biological process essential for health mediated by circadian rhythms, ultradian rhythms (sleep architecture), and homeostatic processes (sleep drive).3
Sleep serves a multitude of functions including:
- cardiometabolic health
- immune enhancement
- brain and body recuperation and restoration
- metabolic regulation
- nervous system connectivity and plasticity
- memory consolidation
- mood and emotional regulation.4-6
The changing sleep environment
The invention of the electric light bulb in the late 19th century has created a seismic shift in how our days and nights are structured. The availability of inexpensive, bright, artificial illumination has extended indoor living, increased shift work and the length of the working day, while reducing the amount of time spent outdoors.7,8
The ability to control the light in our environment has seen a 1.5- 2 hour per night decrease in the average person’s sleep over the last 50 years, according to USA figures.9 Several studies have shown short sleep duration, generally defined as less than 5 or 6 hours a night, is associated with insulin resistance and cardiometabolic health outcomes, including T2DM.6,8
However, short sleep duration is not the only issue. Circadian misalignment (when sleep, feeding, and wake cycles do not match internal circadian rhythms), oversleeping (more than 8 hours a night), and poor sleep quality can also increase the risk of T2DM.1,10
How sleep dysregulation contributes to metabolic dysregulation
Sleep deprivation can lower glucagon levels, inhibiting pancreatic function and reducing the ability to access hepatic glycogen stores effectively.11 Additionally, adipocyte and skeletal muscle become desensitised to insulin.1,8
Disruption of slow-wave sleep can reduce insulin sensitivity by 25%, and decreased slow-wave and REM sleep are linked to poor glucose control.12,13
This sleep loss can stimulate the hypothalamic-pituitary-adrenal axis (HPA), and increase sympathetic nervous system activity, catecholamine production, and cortisol release, while inhibiting insulin secretion, stimulating hepatic gluconeogenesis, and decreasing insulin-mediated glucose uptake by cells.8,10
Appetite and food intake
Lack of sleep can alter neuroendocrine appetite regulation mechanisms and reduce the ability to exert inhibitory control over food. These are mediated primarily by decreases in the satiety hormone leptin and increases in the appetite stimulant ghrelin. This appetite dysregulation can result in an increased consumption of calories and contribute to weight gain and the pathogenesis of T2DM.10,11,14
Decreased physical activity and energy expenditure
In healthy adults with a familial history of T2DM, sleep of less than 5.5 hours per night reduced physical activity by 31% over a 24-hour period.10 Physical activity has been shown to improve insulin sensitivity by increasing glucose uptake in skeletal muscle during exercise and increasing insulin sensitivity post exercise. Daily physical activity is therefore an essential part of metabolic control.1,15
Inflammation
Chronic low-grade inflammation is a well-recognised contributing factor to T2DM.15 Poor quality or lack of sleep increases the production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). It also elevates 24-hour cortisol secretion.8
Circadian dysregulation
Circadian dysregulation affects neuroendocrine and metabolic pathways, increasing T2DM risk. Studies on shift workers show they experience insulin resistance even without sleep restriction, indicating that the cardiometabolic effects of shift work are not solely due to sleep loss.16
Voluntary circadian misalignment is common in non-shift workers due to changes in work habits and lifestyle, with less daylight exposure and more artificial light at night.8
Presence of obstructive sleep apnoea
Obstructive sleep apnoea (OSA) impacts glucose and insulin in multiple ways. The intermittent hypoxia and sleep fragmentation may increase sympathetic nervous stimulation, inflammatory markers such as C-reactive protein (CRP), and alter leptin sensitivity.8 Continuous positive airway pressure (CPAP) is considered a front-line treatment for OSA and has also been shown to improve markers of insulin resistance.19
The impact of sleep and circadian dysregulation on our metabolic health is complex and multifaceted. Supporting healthy sleep habits is vital to reducing the burden of diabetes.
References
1 Saner NJ, Bishop DJ, Bartlett JD. Is exercise a viable therapeutic intervention to mitigate mitochondrial dysfunction and insulin resistance induced by sleep loss ? Sleep Med Rev. 2018;37:60-68.
2 Khan MAB, Hashim MJ, King JK, et al. Epidemiology of type 2 diabetes - Global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10(1):107–11.
3 De Bernardi Rodrigues AM, da Silva C de C, Vasques ACJ, et al. Association of sleep deprivation with reduction in insulin sensitivity as assessed by the hyperglycemic clamp technique in adolescents. JAMA Pediatrics. 2016;170(5):487–94.
4 Kruegar JM, Frank MG, Wisor J, et al. Sleep function: Toward elucidating an enigma. Sleep Med Rev. 2015;28:42-50.
5 Henry M, Thomas KGF, Ross IL. Sleep, cognition and cortisol in Addison’s Disease: A mechanistic relationship. Frontiers in Endocrinology. 2021;12.
6 Dejenie TA, G/Medhin MT, Admasu FT, et al. Impact of objectively-measured sleep duration on cardiometabolic health: A systematic review of recent evidence. Frontiers in Endocrinology. 2022;13.
7 Smolensky MH, Sackett-lundeen LL, Portaluppi F, et al. Nocturnal light pollution and underexposure to daytime sunlight : Complementary mechanisms of circadian disruption and related diseases. Chronobiol Int 2015;32(8):1029-1048.
8 Koren D, Sullivan KLO, Mokhlesi B. Metabolic and glycemic sequelae of sleep disturbances in children and adults. Curr Diab Rep 2015;15(562):1-10.
9 Rice JR, Larrabure-Torrealva GT, Fernandez MAL, et al. High risk for obstructive sleep apnea and other sleep disorders among overweight and obese pregnant women. BMC Pregnancy and Childbirth. 2015;15(1):198.
10 Schmid SM, Hallschmid M, Schultes B. The metabolic burden of sleep loss. Lancet Diabetes Endocrinol [Internet] 2014;8587(14):1-11.
11 Rangaraj VR, Knutson KL. Association between sleep deficiency and cardiometabolic disease: implications for health disparities. Sleep Med 2017;18:19-35.
12 Bliwise DL, Greer SA, Scullin MK, Phillips LS. Habitual and recent sleep durations: Graded and interactive risk for impaired glycemic control in a biracial population. The American Journal of Medicine. 2017;130(5):564–71.
13 Besedovsky L, Cordi M, Wißlicen L, et al. Hypnotic enhancement of slow-wave sleep increases sleep-associated hormone secretion and reduces sympathetic predominance in healthy humans. Commun Biol. 2022;5(1):1–10.
14 Duraccio KM, Whitacre C, Krietsch KN, Zhang N, Summer S, Price M, et al. Losing sleep by staying up late leads adolescents to consume more carbohydrates and a higher glycemic load. Sleep. 2022;45(3):zsab269.
15 Hameed I, Masoodi SR, Mir SA, et al. Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition. World J Diabetes 2015;6(4):598-612.
16 Leproult R, Holmbäck U, Cauter E Van. Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss. Diabetes 2014;12(3):1-35.
17 Sheppard AL, Wolffsohn JS. Digital eye strain: prevalence, measurement and amelioration. BMJ Open Ophthalmology. 2018;3(1):e000146.
18 Singh M, Jadhav HR. Melatonin: Functions and ligands. Drug Discov Today. 2014;19(9):1410-1418.
19 Chen L, Kuang J, Pei JH, et al. Continuous positive airway pressure and diabetes risk in sleep apnea patients: A systemic review and meta-analysis. European Journal of Internal Medicine. 2017;39:39–50.
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